Authors
Hiroshi Mitsumoto, Hélène Blasco, Philippe Corcia, Vincenzo Silani
Published in
Biomolecules. Volume 16. Issue 8. Aug 01, 2026. Epub Aug 01, 2026.
Abstract
Amyotrophic lateral sclerosis (ALS) is a devastating and invariably fatal disease for which currently available disease-modifying therapies provide only modest benefit. Defining its underlying pathogenesis is therefore essential for the development of effective treatments. Increasing evidence indicates that ALS is not restricted to motor neurons but involves multiple neuronal and glial systems, extending to peripheral organs, often at subclinical levels. These multisystem alterations may precede overt neurological symptoms by years and are accompanied by metabolic disturbances, including progressive weight loss and hypermetabolism. In peripheral tissues, ongoing cellular turnover and associated immune and inflammatory responses may further increase energy demand. Within this framework, mitochondrial dysfunction emerges as a central mechanism underlying impaired bioenergetics and systemic metabolic failure. Mitochondria not only regulate energy production but also contribute to oxidative stress, which in turn exacerbates mitochondrial injury, creating a self-amplifying cycle. Importantly, many genetic forms of familial ALS directly affect mitochondrial pathways, and similar biochemical abnormalities are observed in sporadic ALS. These shared features suggest that mitochondrial dysfunction represents a common pathway across ALS subtypes. Targeting upstream mechanisms of mitochondrial impairment may therefore provide a unifying strategy for understanding ALS pathogenesis and developing effective therapies.
PMID:
42650794
Bibliographic data and abstract were imported from PubMed on 14 Oct 2026.
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